Efficacy of Treatments for Opioid-induced Constipation: A Systematic Review and Meta-Analysis.
Clin Gastroenterol Hepatol. 2018 Jan 25;:
Authors: Nee J, Zakari M, Sugarman MA, Whelan J, Hirsch W, Sultan S, Ballou S, Iturrino J, Lembo A
BACKGROUND & AIMS: Opioid induced constipation (OIC) is a common problem in patients on chronic opioid therapy for cancer-related and non-cancer related pain. Approved treatments for OIC are methylnaltrexone, naloxone, naloxegol, alvimopan, naldemedine, and lubiprostone. Since a meta-analysis performed in 2014, 2 new agents have been approved by the Food and Drug Administration (FDA) for treatment of OIC (naloxegol and naldemedine).
METHODS: We conducted a search of the medical literature following the protocol outlined in the Cochrane Handbook for systematic review. We searched MEDLINE, EMBASE, and EMBASE Classic, Web of Science, and the Cochrane Central Register of Controlled Trials until March 2017 to identify randomized controlled trials of peripheral u-opioid receptor antagonists (methylnaltrexone, naloxone, naloxegol, alvimopan, axelopran, or naldemedine), lubiprostone, or prucalopride. Response to therapy was extracted in a dichotomous assessment as an overall response to therapy. The effect of pharmacological therapies was pooled and reported as a relative risk (RR) of failure to respond to the treatment drug, with 95% CIs.
RESULTS: We included 27 placebo-controlled trials in our meta-analysis (23 trials evaluated μ-opioid receptor antagonists, 3 trials evaluated lubiprostone, and 1 trial evaluated prucalopride). In these trials, 5390 patients received a drug and 3491 received a placebo. Overall, μ-opioid receptor antagonists, lubiprostone, and prucalopride were superior to placebo for the treatment of OIC, with a RR of failure to respond to therapy of 0.70 (95% CI, 0.64-0.75) and an overall number needed to treat of 5 (95% CI, 4-7). When restricted to only FDA-approved medications for OIC, the RR of failure to respond to therapy was the RR was 0.69 (95% CI, 0.62-0.77) with a number needed to treat of 5 (95% CI, 4-7). Sensitivity analyses and meta-regression performed to account for heterogeneity showed that treatment was more likely to be effective in study populations taking higher doses of opiates at baseline or refractory to laxatives. Study duration and pre-specified primary outcome did not affect the RR of failure. Participants who received μ-opioid receptor antagonists were significantly more likely to have diarrhea, abdominal pain, nausea, or vomiting than patients who received placebo.
CONCLUSION: In a systematic review and meta-analysis, we found μ-opioid receptor antagonists to be safe and effective for the treatment of OIC. Prescription-strength laxatives (prucalopride, lubiprostone) are slightly better than placebo in reducing OIC.
PMID: 29374616 [PubMed - as supplied by publisher]